Phenolic compounds: current industrial applications, limitations and future challenges

Phenolic compounds are natural bioactive molecules found mainly in plant tissues that have shown interesting bioactivities, such as antioxidant, antimicrobial, anti-inflammatory, and antiproliferative activities, among others, which has led to great interest in their use by several industries. However, despite the large number of scientific studies on this topic, some issues still need to be studied and solved, such as the understanding of the main actions of these compounds in organisms. Besides their large potential applicability in industry, phenolic compounds still face some issues making it necessary to develop strategies to improve bioavailability, sustainable technologies of extraction and refinement, and stability procedures to increase the range of applicability. This review focuses on the most recent advances in the applications of phenolic compounds in different technological and medicinal areas. In addition, techniques to improve their sustainable resourcing, stability and bioavailability will be presented and discussed. This journal isFoundation for Science and Technology (FCT, Portugal) is acknowledged for financial support by national funds FCT/ MCTES to CIMO (UIDB/00690/2020). National funding by FCT, P. I., through the institutional scientific employment programcontract for Lillian Barros contract and through the individual scientific employment program-contract for Sandrina A. Heleno, and B. Albuquerque Research grant (SFRH/BD/136370/2018 ). European Regional Development Fund (ERDF) through the Regional Operational Program North 2020, within the scope of Project NORTE-01-0145-FEDER-023289: DeCodE and project Mobilizador Norte-01-0247-FEDER-024479: ValorNatural®. FEDER-Interreg España-Portugal programme is acknowledged for financial support through the project 0377_Iberphenol_6_E.info:eu-repo/semantics/publishedVersio

Extraction of rosmarinic acid from Melissa officinalis L. by heat-, microwave- and ultrasound-assisted extraction techniques: A comparative study through response surface analysis

The goal of this study was to compare the extraction of rosmarinic acid from Melissa officinalis L. using three techniques (heat- -, microwave- and ultrasound- assisted extraction). In order to obtain the conditions that maximize the rosmarinic acid extraction, a response surface methodology was applied using the circumscribed central composite design of three variables with five levels. The relevant independent variables used for the process optimization were time, temperature and ethanol–water proportion for heat-assisted- and microwave-extration, whereas for the ultrasound method the ultrasonic power was variable. The responses used as criteria were the amount of rosmarinic acid was determined by HPLC-DADand the extraction yield of the obtained residue. Ultrasound extraction proved to be the most effective method, capable of yielding 86.3 ± 4.1 mg rosmarinic acid/g plant per dry weight (dw) at the optimal extraction conditions (33.0 ± 3.2 min, 371.7 ± 19.3 W and 39.9 ± 1.4% of ethanol). According to the content of rosmarinic acid, microwave- and heat-assisted extractions techniques were less effective, producing 49.4 ± 2.3 (at 26.5 ± 2.1 min, 108.6 ± 10.2 °C and 25.5 ± 0.9% of ethanol) and 59.4 ± 2.2 (at 106.2 ± 5.1 min, 88.0 ± 2.9 °C and 34.5 ± 1.6% of ethanol), respectively. Additionally, the solid/liquid ratio effect at the optimal values in a dose–response format was studied in view of its plausible transference at industrial level, showing a decreasing non-linear pattern from 5 to 120 g/L. In brief, the obtained results highlight the potential applications of using the leaves from M. officinalis as a source of rosmarinic acid.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2013), REQUIMTE (UID/QUI/50006/2013 - POCI/01/0145/ FEDER/007265) and Caleja (SFRH/BD/93007/2013) and L. Barros (SFRH/BPD/107855/2015) grants. This work was also financially supported by: Project POCI-01-0145-FEDER-006984 – Associate Laboratory LSRE-LCM funded by FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) – and by national funds through FCT - Fundação para a Ciência e a Tecnologia. To Xunta de Galicia for financial support for the post-doctoral researcher of M.A. Prieto. The authors also thank to company Mais Ervas, Lda (Alfandega da Fé, Portugal), for providing the M. officinalis samples.info:eu-repo/semantics/publishedVersio

Development of a natural preservative obtained from male chestnut flowers: Optimization of a heat-assisted extraction technique

The aim of this work was to optimize the conditions for the extraction of phenolic compounds (PC) from male chestnut flowers using heat-assisted extraction in developing extracts rich in PC for potential industrial application as a natural ingredient. The study conditions of time (t), temperature (T), solvent (S, water-ethanol mixtures) and solid-to-liquid ratio (S/L) were optimized. The responses used were obtained from the quantification of the fourteen major individual PC identified by HPLC-DAD-ESI/MS (seven hydrolysable tannins and seven flavonoids). The recovery of hydrolysable tannins was higher than that of flavonoids, with trigalloyl-HHDP-glucoside being the major one. The conditions that maximized the PC content were t = 20.0 ± 37.7 min, T = 25.0 ± 5.7 °C, S = 0.0 ± 8.7% ethanol and S/L = 82.8 g L -1 , producing an extract with 86.5 mg PC g -1 of extract. The results highlight the potential of valorising chestnut flower agro-residues as a productive source of PC for the development of bio-based ingredients for food/pharmaceutical/cosmeceutical industrial applications able to compete with synthetic compounds.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER under Programme PT2020 for providing financial support to CIMO (UID/AGR/ 00690/2013), a Caleja (SFRH/BD/93007/2013) grant, and an L. Barros contract. The authors are also grateful to the FEDER-Interreg España-Portugal programme for financial support through the project 0377_Iberphenol_6_E; to the European Regional Development Fund (ERDF) through the Regional Operational Program North 2020, within the scope of Project NORTE-01-0145-FEDER-023289: DeCodE. The authors thank the GAIN (Xunta de Galicia) for providing financial support (P.P. 0000 421S 140.08) to M.A. Prieto through a postdoctoral (modality B) graninfo:eu-repo/semantics/publishedVersio

Cold extraction of phenolic compounds from watercress by high hydrostatic pressure: Process modelling and optimization

High hydrostatic pressure (HHP) was applied to the extraction of phenolic compounds from watercress (Nasturtium officinale). The process was optimized by response surface methodology using a five-level central composite design combining the independent variables of processing time (t, 1.5–33.5 min), pressure (P, 0.1–600 MPa) and solvent (S, 0–100% of ethanol, v/v). The individual and grouped phenolic compounds, analyzed by HPLC-DAD-ESI/MS, and the extraction yield were used as response variables. The theoretical models were fitted to the experimental data, statistically validated, and used in the prediction and optimization steps. The optimal HHP conditions for the extraction of phenolic compounds were: t = 3.1 min, P = 600 MPa and S = 100%, and originated 64.68 ± 2.97 mg/g of extract. This study highlighted the HHP as a promising technology to cold extract phenolic compounds (phenolic acids and flavonoids) from watercress in a selective way using a green solvent and reduced extraction times.info:eu-repo/semantics/publishedVersio

Microwave-assisted extraction of phenolic acids and flavonoids and production of antioxidant ingredients from tomato: a nutraceutical-oriented optimization study

The production of natural extracts requires suitable processing conditions to maximize the preservation of the bioactive ingredients. Herein, a microwave-assisted extraction (MAE) process was optimized, by means of response surface methodology (RSM), to maximize the recovery of phenolic acids and flavonoids and obtain antioxidant ingredients from tomato. A 5-level full factorial Box-Behnken design was successfully implemented for MAE optimization, in which the processing time (t), temperature (T), ethanol concentration (Et) and solid/liquid ratio (S/L) were relevant independent variables. The proposed model was validated based on the high values of the adjusted coefficient of determination and on the non-significant differences between experimental and predicted values. The global optimum processing conditions (t=20 min; T=180 ºC; Et=0 %; and S/L=45 g/L) provided tomato extracts with high potential as nutraceuticals or as active ingredients in the design of functional foods. Additionally, the round tomato variety was highlighted as a source of added-value phenolic acids and flavonoids.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support to CIMO (PEst-OE/AGR/UI0690/2014), REQUIMTE (UID/QUI/50006/2013 - POCI/01/0145/FERDER/007265), J. Pinela (SFRH/BD/92994/2013) and L. Barros (SFRH/BPD/107855/2015); FCT/MEC and FEDER under Programme PT2020 for financial support to LSRE (UID/EQU/50020/2013), and to QREN, ON2 and FEDER (NORTE-07-0162-FEDER-000050); to the Xunta de Galicia for financial support for the post-doctoral researcher of M.A. Prieto

Ellagitannin-rich bioactive extracts of Tuberaria lignosa: insights into the radiation-induced effects in the recovery of high added-value compounds

Ellagitannins are polyphenols responsible for a number of bioactivities and health-promoting effects. These industrially important molecules can be affected by post-harvest treatments and recovery processes, but little is known about the irradiation-induced effects on their integrity, bioactivity and extractability. Herein, the impact of gamma radiation on the production of ellagitannin-rich extracts was investigated using Tuberaria lignosa as a case study. These effects were compared with those induced in flavonoids and organic acids. The extracts were particularly rich in hydrophilic antioxidants (measured by in vitro assays). The recovery of different phytochemicals was favoured by longer extraction times. Ellagitannins (mainly punicalagin derivatives) were extracted better from samples irradiated at 5 kGy and were not significantly affected by the 10 kGy dose. However, the total contents of flavonoids and organic acids were decreased by the consequent increase in irradiation dose. Therefore, this study supports the use of gamma radiation for processing T. lignosa, aiming to obtain ellagitannin-rich bioactive extracts.The authors are grateful to the PRODER research project no. 53514 AROMAP for financial support of the work; to the Foundation for Science and Technology (FCT) of Portugal and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2013); to FCT/MEC for financial support to REQUIMTE/LAQV (UID/QUI/50006/2013 - POCI/01/ 0145/FERDER/007265); to FCT for the grants attributed to J. Pinela (SFRH/BD/92994/2013; funded by the European Social Fund and MEC through Programa Operacional Capital Humano (POCH)) and L. Barros (SFRH/BPD/107855/2015); to the Xunta de Galicia for financial support to M. A. Prietoinfo:eu-repo/semantics/publishedVersio

Gamma radiation-induced effects on the recovery of pharmacologically active polyphenols from tuberaria lignosa medicinal plant

Ionizing radiation has been used for many years as a safer and environmentally friendly alternative comparatively to chemical fumigants to decontaminate medicinal plants and other food commodities [1]. Perennial spotted rockrose (Tuberaria lignosa (Sweet) Samp.) is a highly quoted medicinal plant in the northeast region of Portugal rich in ellagitannin derivatives [2,3]. As polyphenols, these compounds play an important role in human nutrition and display several biological effects, including antioxidant, anti-inflammatory, antitumor, antibacterial, and anti-HIV replication activities [2-4]. However, little is known about the impact of ionizing radiation on the integrity and extractability of these high added-value compounds. This work aimed to investigate the effects of γ-rays irradiation on the extraction and/or degradation kinetics of ellagitannins from T. lignosa aerial parts. The plant material was submitted to irradiation doses up to 10 kGy in a cobalt-60 experimental chamber. Then, the non-irradiated and irradiated plant material was submitted to different solid-liquid extractions, according to a three-level full factorial design, using boiling water as extraction solvent. The ellagitannins were analyzed in a high-performance liquid chromatography (HPLC) system connected to a diode array detector (DAD) and a mass spectrometer (MS). Punicalin, punicalagin isomers, and punicalagin gallate isomers were the most abundant compounds. In general, the extractability of this group of phytochemicals was improved by the irradiation treatment (5 kGy) and longer extraction times (10 min). In addition, the 10 kGy dose did not induced adverse effects. In conclusion, this study demonstrated the suitability of γ-rays irradiation for preserving or improving the extractability of pharmacologically active compounds from T. lignosa aerial parts.The authors are grateful to the Foundation for Science and Technology (FCT) of Portugal and FEDER, under Programme PT2020, for financial support to CIMO (UID/AGR/00690/2013); to FCT/MEC for financial support to REQUIMTE/LAQV (UID/QUI/50006/2013 - POCI/01/0145/FEDER/007265); to FCT for the J. Pinela grant (SFRH/BD/92994/2013) and L. Barros contract; to the Xunta de Galicia for financial support to M. A. Prieto; C2TN (RECI/AAG-TEC/0400/2012 and UID/Multi/04349/2013 projects); International Atomic Energy Agency (IAEA - CRP D61024 - DEXAFI). The authors are also grateful to the Interreg España-Portugal for financial support through the Project 0377_Iberphenol_6_E.info:eu-repo/semantics/publishedVersio

Nutritional and bioactive oils from salmon (Salmo salar) side streams obtained by Soxhlet and optimized microwave-assisted extraction

The efficiency of the microwave-assisted extraction (MAE) technique on recovering nutritional and bioactive oils from salmon (Salmo salar) side streams was evaluated and compared to Soxhlet extraction. The response surface methodology (RSM) coupled with a central composite rotatable design was used to optimize time, microwave power, and solid/liquid ratio of the MAE process in terms of oil yield. The optimal MAE conditions were 14.6 min, 291.9 W, 80.1 g/L for backbones, 10.8 min, 50.0 W, 80.0 g/L for heads, and 14.3 min, 960.6 W, 99.5 g/L for viscera, which resulted in a recovery of 69% of the total lipid content for backbones and heads and 92% for viscera. The oils obtained under optimal MAE conditions showed a healthy lipid profile as well as cytotoxic, antioxidant, anti-inflammatory, or antimicrobial properties. These results highlight that oils from underutilized salmon by-products could be exploited by different industrial sectors under the circular economy approach.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020). To FCT for the contracts of J. Pinela (CEECIND/01011/2018) and L. Barros (through the institutional scientific employment program-contract). This work was funded by the European Regional Development Fund (ERDF) through the Competitiveness and Internationalization Operational Program (POCI), within the scope of project HealthyPETFOOD (POCI-01-0247-FEDER-047073), and by BBI-JU through the H2020 Project AQUABIOPRO-FIT “Aquaculture and agriculture biomass side streams proteins and bioactives for feed, fitness, and health promoting nutritional supplements” (Grant number 790956).info:eu-repo/semantics/publishedVersio

Fig “Ficus carica L.” and its by-products: A decade evidence of their health-promoting benefits towards the development of novel food formulations

The food industry constantly searches for natural derived bioactive molecules with preventive and therapeutic effects using innovative and sustainable strategies. Fig production and processing generate a considerable amount of by-products (leaves, pulp, peels, seeds, and latex) with limited commercial exploitation and negative impact on the environment. These by-products are important sources of high value-added in- gredients, including anthocyanins and pectins that can be of particular interest to the food industry as functional colourants, emulsifiers, and additives. Scope and approach: This review curates recent advances in the valorisation of fig by-products as valuable sources of bioactive molecules for functional food development. Special attention was given to widely used extraction processes, main bioactive compounds, relevant biological properties, and the application of recovered bioactives for functional food development. Key findings and conclusions: Fig by-products are essential sources of structurally diverse bioactive molecules with unique antidiabetic, anti-inflammatory, anti-tumour, immunomodulatory and cardioprotective properties. Owing to these health-promoting potentials, an integral valorisation approach involving sustainable technologies to recover these high value-added ingredients and its utilisation in novel food formulation development should be further stimulated.Funding for open access charge: Universidade de Vigo/CISUG. Au- thors are grateful to Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to the CIMO (UIDB/00690/2020). L. Barros, thank the national funding by FCT, P.I., through the institutional scientific employment program for her contract. This work is also supported by MICINN supporting the Ramo ́n y Cajal grant for M.A. Prieto (RYC-2017-22891) and Juan de la Cierva Formacio ́nn contract for T. Oludemi (FJC2019-042549-I) and by Xunta de Galicia for supporting the program EXCELENCIA-ED431F 2020/12 and the pre-doctoral grant of M. Carpena (ED481A 2021/ 313). Manuel Ayuso thanks to PRIMA and FEDER-Interreg Espan ̃a- Portugal programme for financial support through the projects Local- NutLeg (Section 1 2020 Agrofood Value Chain topic 1.3.1). This work is also supported by the project SYSTEMIC Knowledge hub on Nutrition and Food Security, which received funding from national research funding entities in Belgium (FWO), France (INRA), Germany (BLE), Italy (MIPAAF), Latvia (IZM), Norway (RCN), Portugal (FCT), and Spain (AEI) in a joint action of JPI HDHL, JPI-OCEANS and FACCE-JPI launched in 2019 under the ERA-NET ERA-HDHL (n◦ 696295). Authors are grateful to Ibero-American Program on Science and Technology (CYTED—AQUA-CIBUS, P317RT0003), to the Bio Based Industries Joint Undertaking (JU) under grant agreement No 888003 UP4HEALTH Project (H2020-BBI-JTI-2019) The JU receives support from the Euro- pean Union’s Horizon 2020 research and innovation program and the Bio Based Industries Consortium. This work has also received financial support from Portuguese national funds (Fundação para a Ciência e Tecnologia e Ministério da Ciência, Tecnologia e Ensino Superior, FCT/ MCTES) through project UIDB/50006/2020 and AgriFood XXI I&D&I project (NORTE-01-0145-FEDER-000041) cofinanced by European Regional Development Fund (ERDF), through the NORTE 2020 (Programa Operacional Regional do Norte 2014/2020).info:eu-repo/semantics/publishedVersio

Sea bass (Dicentrarchus labrax) and sea bream (Sparus aurata) head oils recovered by microwave-assisted extraction: nutritional quality and biological properties

Microwave-assisted extraction (MAE) and Soxhlet extraction (SE) were used to obtain oil from European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata) heads. The MAE technique allowed the recovery of more than 50% of the total lipid con- tent for both fish by-products in less than 11 min extraction. Based on their fatty acid composition, all fish head oils presented a healthy lipid profile and were found to be a good source of docosahexaenoic acid (DHA, 11–14%). Different lipid quality indices also revealed their cardiovascular protective potential. Oils obtained by MAE showed higher antibacterial and antifungal effects against food pathogens than those extracted by SE. Cellular antioxidant activity (29–35% oxidation inhibition) and anti-inflammatory poten- tial via NO production inhibition (IC50 = 14–21 μg/mL) were evaluated using murine macrophages cells (RAW 264.7). The highest cytotoxic effect (GI50 = 38–46 μg/mL) of fish head oils was observed against breast cancer cells (MCF-7). These results showed that sea bass and gilthead sea bream heads could be exploited for the production of oil with nu- tritional and bioactive properties in line with circular bioeconomy concepts.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020). To FCT for the contracts of J. Pinela (CEECIND/01011/2018) and L. Barros (institutional scientific employment program-contract). Work funded by the European Regional Development Fund (ERDF) through the Competitiveness and Internationalization Operational Program (POCI), within the scope of project HealthyPETFOOD (POCI-01-0247-FEDER- 047073), and by BBI-JU through the H2020 Project AQUABIOPRO-FIT “Aquaculture and agriculture biomass side streams proteins and bioactives for feed, fitness, and health promoting nutritional supplements” (Grant number 790956)info:eu-repo/semantics/publishedVersio